EvoMuse MyoSynergy Write-up

We're just brushing up against the scientific density of this product. I'm really excited for this release - it has been a long time in the making.

MyoSynergy Write Up

MyoSynergy is a brand new, unique formula designed to potently trigger multiple pathways of muscle building at the cellular level. In addition, it will also aid in preventing muscle breakdown, boosting strength levels, and encouraging mitochondrial biogenesis.

To better understand the inclusion of the specific ingredients in the formula, it is important to have a little bit of background on the ways the body upregulates muscle growth. We don't just grow or shrink unless we have the proper signals to do so. The primary growth signal, and the main anabolic focus of MyoSynergy, is the PI3K/AKT/mTOR pathway.

Anabolic/Catabolic Signaling

To trigger anabolism, the body primarily engages in the following sequence of events:

Insulin Like Growth Factor 1 (IGF1) activates Phosphoinositide 3-Kinase (PI3K), which activates Protein Kinase B (Akt), which then activates the Mechanistic Target of Rapamycin (MTOR, also known as the mammalian Target of Rapamycin). Considered the master regulator of protein synthesis in muscle, MTOR is the key player in this cascade.

Although it was previously thought that Myostatin generated a cellular signal to kickstart muscle breakdown, it has now been shown to instead block the above anabolic pathway (1,2). So inhibition of myostatin allows for accelerated anabolism.

Catabolic Signaling is multifaceted and complex, but a couple of key players in the triggering of muscle protein degradation are MuRF1 and MAFbx (3–5). These can be activated by inflammatory cytokines like TGF-a and NF-kappaB, but are also susceptible to other mechanisms of activation (6).

Now with this background out of the way, let's get into how MyoSynergy will favorably manipulate these pathways to greatly augment your ability to gain muscle!

Astragalus Membranaceus 20:1

While Astragalus Membranaceus (AM) has numerous potential benefits, here we are focused on a few specific ones, namely IGF1 boosting, Myostatin inhibition, glucose and insulin signaling, and exercise performance.

AM has been shown to upregulate IGF1 production, which, as noted above, kickstarts the entire anabolic cascade (7). Researchers later conducted a study to re-test this, and found that it did in fact increase IGF1 while also stimulating bone growth in rats, and suggested that AM "may be helpful in stimulating growth in children with short stature", which it is actually used for in traditional Korean medicine (8). In fully-grown adults, IGF1 is no longer responsible for bone growth, as it shifts its focus to other duties like muscle growth. So, sorry, MyoSynergy will not make you taller, you'll just have to distract people with your bigger muscles.

As you recall from earlier, IGF1 activation is going to indirectly decrease Myostatin levels. In addition to that, another study showed that AM was able to reduce Myostatin more directly by inhibiting the NF-kappaB pathway (9).

Aside from boosting IGF1 to enhance anabolism, AM also appears to have a pronounced effect on the way the body handles glucose and insulin. In one study, when researchers tried to fatten rats up and give them diabetes, AM was able to ameliorate "glucose toxicity", improve insulin sensitivity, and increase glucose uptake in the muscle cells (10). This boost in insulin sensitivity and increased muscle glycogen storage has been corroborated by other studies as well (9,11,12). Better skeletal muscle insulin sensitivity and more glucose uptake = bigger muscles. Nice.

AM has also been shown to enhance exercise performance by reducing the accumulation of metabolic waste products (11).

(-)Epicatechin

(-)Epicatechin is an exciting ingredient with potential to stimulate muscle growth through multiple avenues.

As we age, Myostatin increases while its inhibitors like follistatin and myogenin/MyoD (the latter two are responsible for regulating muscle cell differentiation) tend to decrease. This sets the stage for increased muscle loss. (-)Epicatechin has been shown to reverse this, decreasing Myostatin and improving the follistatin/myostatin ratio and increasing strength after only seven days of intake (13). As well, MyoStatin expression is one of the major limiting factors in muscle growth for people of all ages. Inhibition of MyoStatin by MyoSynergy should result in increased muscle growth rates for all users.

(-)Epicatechin has also been shown in multiple studies to increase muscle capillarity and biogenesis of mitochondria, which persists even with cessation of use (14,15). More blood flow and mitochondria paves the road to enhanced hypertrophic capability and improved performance. In addition, (-)epicatechin has recently been shown to favorably regulate the function of specific proteins in control of muscular contraction (16).

HICA

HICA stands for Hydroxyicocaproic Acid, also known as Leucic Acid, and is a metabolite of the main MTOR activating amino acid L-Leucine. When you ingest Leucine, it goes down one of two metabolic pathways and either converts to KIC or HMB. If it gets converted to KIC, some of that gets converted to HICA. Now the problem with this traditional conversion cascade, is that KIC upregulates an enzyme called BCKDH, which then oxidizes BCAA's including Leucine, so it acts as a governor on the available Leucine pool in the bloodstream, eventually using it all up to halt MTOR activation. One of the main reasons people can get away with a lower protein intake on a ketogenic diet and still build muscle is because in ketosis, the body oxidizes (wastes) less Leucine, so each gram of protein is more anabolic. Now, this still needs to be shown in research, but theoretically HICA can sneak by the regulatory mechanisms that trigger BCKDH, therefore allowing more MTOR activation before the party gets shut down.

A recent study published in the highly respected ISSN Journal looked at the effect of HICA supplementation for four weeks in male soccer players. The results showed an increase in lean body mass, 23% reduction in DOMS, and improved training alertness in the HICA group compared to placebo (17). A full daily dose of MyoSynergy exceeds the 1.5g of HICA used in this study.

Another study performed on rats placed into casts analyzed the effect on both immobility induced atrophy and post removal protein synthesis. While the HICA didn’t prevent the atrophy, recovery was remarkably sped up to precasting rates in the HICA treated animals. Accelerated protein synthesis rates from HICA administration were indicated (35)

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ATP
Previous research has led people to believe that adenosine triphosphate (ATP) is not orally bioavailable, thus dismissing its use as a sports supplement (18). While the research itself was not inherently incorrect, it turns out researchers were just measuring ATP at the wrong place (they should have been measuring venous portal blood). Since we now know more about the kinetics of oral ATP, it turns out the most effective time to ingest it is about 30 minutes pre-workout, so be sure to time one of your MyoSynergy doses accordingly.

Before the more accurate testing methods were elucidated, a study was conducted that looked at the effect of ATP supplementation on strength training, and the results were a little surprising considering ATP's apparent lack of oral bioavailability. They found some interesting within group differences in the subject group taking a higher dose of ATP compared to the lower dose group, and concluded supplementation may provide some ergogenic benefits (19).

Broccoli Sprout
Broccoli Sprout is a source of sulforaphane, which has numerous beneficial effects on general health, such as acting as a histone deacetylase inhibitor (21). It also acts as an antioxidant, and more specifically, modulates the redox environment in muscle cells to control exercise induced muscle damage (22,23).

The main reason for inclusion of Broccoli Sprout, however, is the interaction with Myostatin. A recent study in the journal Epigenetics showed that sulforaphane significantly suppresses Myostatin, while also suppressing the negative feedback inhibitors of the Myostatin pathway (21).

Forskolin
Forskolin is well known to induce cyclic AMP production, which has several physiological effects. One of those effects is an increase in follistatin, which, as mentioned previously, counteracts the inhibitory effects of Myostatin on muscle growth (24,25). This cAMP activation has also been shown to directly activate MTOR by phosphorylating S6K1, mobilizing intracellular calcium stores and increasing ATP production (26).

Forskolin has also been shown to enhance the PI3K/Akt pathway, triggering anabolism as well as angiogenesis (the creation of new blood vessels) (27,28).
Cholecalciferol
The final ingredient in MyoSynergy is Cholecalciferol, better known as Vitamin D3. Rates of Vitamin D deficiency continue to climb as people fear sun exposure and consume more nutrient devoid foods, a 2011 study showed that over 40% of the population was Vitamin D deficient, with certain ethnic groups being significantly higher (29). Aside from a multitude of health problems related to suboptimal Vitamin D status, it could also end up being a limiter of muscle growth, even at levels not considered to be an actual deficiency.

A 2013 study looking at healthy, active subjects given supplemental Vitamin D3, showed that they increased peak isometric force and had decreased muscle damage biomarkers…and here's the kicker, they all had clinically sufficient Vitamin D status prior to supplementation (30).

In a study looking at European Sea Bass, the researchers found the group with the highest supplemental Vitamin D3 dosage experienced muscle cell hyperplasia, showing a direct effect of cholecalciferol on muscle cell growth (31). Another 2013 study in human subjects found that supplemental cholecalciferol caused improvements in several tested parameters of muscle strength (32)

In a group of people with low Vitamin D staus, supplemental cholecalciferol was shown to increase the concentration of the Vitamin D Receptors (VDR) by 30%, as well as actual muscle fiber size by 10% (33). Another study showed the same effect of cholecalciferol supplementation to increase VDR concentration, as well as decrease exercise induced muscle damage and inflammation by decreasing NF-kappaB (which could indirectly decrease Myostatin production) (34).

In summary, MyoSynergy is designed to potently upregulate the body's main anabolic signals, inhibit catabolic pathways, and promote increases in strength and exercise performance. The specific combination and dosages of these novel ingredients should allow users to tap into a previously unattainable level of muscle growth.

I have come to realise Australia has a habit of banning any products which are effective, but I will keep my fingers crossed for this one as there does not seem to be any banned substances in it! Will definitely give it a try when its available.